Way to Target Genes Devised for Gene Therapy

Sir Aaron explains: "The beauty of zinc-finger nucleases lies in their simplicity. Where other methods are long, arduous, and often messy, it is relatively easy to switch off genes using this method.”

As reported in the Telegraph, a way to carry out genetic surgery has been devised by a British Nobel prizewinner that is already under test on diabetic patients and being readied for use to treat AIDS, blocked blood vessels, and chronic pain.

So called gene therapy was hailed as a medical revolution two decades ago but progress has been slow, the successes have been hard to come by, and there have been a few deaths.

One key problem is that it has been hard to control where newly introduced genes end up in the genetic makeup of the patient - one fear is that they damage existing genes, or the way they are used.

Now Sir Aaron Klug (pictured), a Nobel laureate working at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, has developed a more efficient way to target genes, so gene therapy can be done with surgical precision.

His team reports a new application of the gene fingers that it has modified: A piece of natural cellular machinery called "zinc fingers."

These are zinc-containing proteins that bind to DNA and control how the genetic code - and the genes it contains - are read in our cells, so that a liver cell is different from a brain cell.

They have devised synthetic versions, called zinc-fingered nucleases, which have the capacity to recognize specific sequences of DNA which makes them extremely good at latching onto a specific spot, targeting particular genes without affecting others, so they can carry out genetic surgery to knock out genes or introduce new ones.

The new method is already being tested on more than 100 young diabetic patients who have lost sensation, a common complication, by the Californian company Sangamo BioSciences. Clinical trials began after obtaining encouraging results in preliminary tests of the method to introduce a gene encoding a growth factor that can help restore sensation.

The work, backed by the Juvenile Diabetes Research Foundation, will be extended to see if it can help treat spinal injury.

Animal trials are already underway to use the same targeted gene therapy to reduce chronic pain and to knock out a gene called CCR5, the docking point used by the HIV to invade white blood cells, called T-cells, in AIDS patients. The trials will lead to a supply of non-infectable T-cells, which will combat HIV and the other infections which occur in AIDS patients.

Clinical trials are also in progress for stimulating the growth of new arteries in patients suffering from obstruction of the blood vessels in the limbs, which can lead to gangrene and amputations.
The new study shows they are effective at knocking out harmful genes too, also a fundamental tool for animal research to work out what genes do.

Sir Aaron explains: “The beauty of zinc-finger nucleases lies in their simplicity. Where other methods are long, arduous, and often messy, it is relatively easy to switch off genes using this method. The zinc-finger design allows us to target a single gene, while the nuclease disrupts the gene. The single step process is extremely quick and reliable and opens up exciting possibilities for research and gene therapy.”